Molecular responses in the telomere-mitochondrial axis of ageing in the elderly: A candidate gene approach
Abstract
Experimental evidence shows that telomere shortening induces mitochondrial damage but so far studies in humans are scarce. Here, we investigated the association between leukocyte telomere length (LTL) and mitochondrial DNA (mtDNA) content in elderly and explored possible intermediate mechanisms by determining the gene expression profile of candidate genes in the telomere-mitochondrial axis of ageing. Among 166 non-smoking elderly, LTL, leukocyte mtDNA content and expression of candidate genes: sirtuin1 (SIRT1), tumor protein p53 (TP53), peroxisome proliferator-activated receptor γ-coactivator1α (PGC-1α), peroxisome proliferator-activated receptor γ-coactivator1β (PGC-1β), nuclear respiratory factor 1 (NRF1) and nuclear factor, erythroid 2 like 2 (NRF2), using a quantitave real time polymerase chain assay (qPCR). Statistical mediation analysis was used to study intermediate mechanisms of the telomere-mitochondrial axis of ageing. LTL correlated with leukocyte mtDNA content in our studied elderly (r = 0.23, p = 0.0047). SIRT1 gene expression correlated positively with LTL (r = 0.26, p = 0.0094) and leukocyte mtDNA content (r = 0.43, p < 0.0001). The other studied candidates showed significant correlations in the telomere-mitochondrial interactome but not independent from SIRT1. SIRT1 gene expression was estimated to mediate 40% of the positive association between LTL and leukocyte mtDNA content. The key finding of our study was that SIRT1 expression plays a pivotal role in the telomere-mitochondrial interactome.
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MtDNA copy number varies during aging and might be considered a biomarker that mirrors alterations within the aged human body.
“MtDNA copy number also varies during aging and might be considered a biomarker that mirrors alterations within the aged human body [34,35,36].”
From Role of Age-Related Mitochondrial Dysfunction in Sarcopenia (2020) · cites this paper as [34]
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Gunnar, M. R. (2021) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.737847338.793583368
Additional file 3 of Interrelationships and determinants of aging biomarkers in cord blood
Reimann, B., Martens, D. S., Wang, C., Ghantous, A., Herceg, Z., Plusquin, M., & Nawrot, T. S. (2022) · Figshare · doi:10.6084/m9.figshare.20462317
Self-citationAdditional file 4 of Interrelationships and determinants of aging biomarkers in cord blood
Reimann, B., Martens, D. S., Wang, C., Ghantous, A., Herceg, Z., Plusquin, M., & Nawrot, T. S. (2022) · Figshare · doi:10.6084/m9.figshare.20462320
Self-citationAdditional file 2 of Interrelationships and determinants of aging biomarkers in cord blood
Reimann, B., Martens, D. S., Wang, C., Ghantous, A., Herceg, Z., Plusquin, M., & Nawrot, T. S. (2022) · Figshare · doi:10.6084/m9.figshare.20462314
Self-citationAdditional file 1 of Interrelationships and determinants of aging biomarkers in cord blood
Reimann, B., Martens, D. S., Wang, C., Ghantous, A., Herceg, Z., Plusquin, M., & Nawrot, T. S. (2022) · Figshare · doi:10.6084/m9.figshare.20462311
Self-citationAdditional file 5 of Interrelationships and determinants of aging biomarkers in cord blood
Reimann, B., Martens, D. S., Wang, C., Ghantous, A., Herceg, Z., Plusquin, M., & Nawrot, T. S. (2022) · Figshare · doi:10.6084/m9.figshare.20462323
Self-citationA novel approach for age estimation based on blood mitochondrial DNA analysis
Wen, J., Yu, X., Zhao, W., Sui, S., Xu, J., Zhao, J., Liu, R., Li, M., Zhou, P., Wei, R., et al. (2026) · International Journal of Legal Medicine · doi:10.1007/s00414-026-03778-1
- Authors
- Pieters, N., Janssen, B. G., Valeri, L., Cox, B., Cuypers, A., Dewitte, H., Plusquin, M., Smeets, K., & Nawrot, T. S.
- Affiliations
- Hasselt University (BE)
- Harvard University (US)
- Corresponding author
- Nawrot, Tim S.
- ORCID
- Venue
- Mechanisms of Ageing and Development
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 145
- Pages
- 51-57
- ISSN
- 0047-6374 (ISSN-L)
- OpenAlex
- W2077438828
- Cited by
- 43
- References
- 53
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 8 · 2021: 3 · 2020: 4 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 1 · 2015: 3
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Mechanisms of Ageing and Development (publishedVersion)
- PubMed (publishedVersion)
- Document Server@UHasselt (UHasselt) (submittedVersion)
- Lirias (submittedVersion)
- Funders
- Flemish Scientific Fund (G.0880.13/G.0783.11.N.10)
- European Research Council (ERC310898)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- telomere shortening, mitochondrial DNA content, aging, older adults, leukocyte telomere length, SIRT1, sirtuins, PGC-1α, PGC-1β, NRF1, Nrf2, TP53, gene expression, mediation analysis
- MeSH terms
- Aged, Aging, DNA, Mitochondrial, Female, Gene Expression Regulation, Humans, Leukocytes, Male, Telomere, Telomere Homeostasis
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